Cryptosporidiosis is a devastating disease in immunodeficient hosts caused by Cryptosporidium parvum, a sporozoan parasite that replicates in the epithelial cells of the intestinal and/or respiratory tract of man and other mammals. Infection of immunocompetent hosts results in self-limiting gastrointestinal symptoms, followed by recovery and resistance to reinfection, in most cases. In contrast, immunodeficient patients, including those with AIDS, experience persistent infection accompanied by chronic, life-threatening diarrhea. Persistence of infection in immunodeficient patients is explained by 1) absence of chemotherapeutic agents effective against C. parvum, 2) absence of effective immune responses required to terminate infection, and 3) the existence of two autoinfective loops in the life cycle of C. parvum, which allows sporozoites and merozoites to infect additional host epithelial cells in the absence of new exposure to an exogenous source of the organism. In 1987, we responded to RFA 87-AI-07, """"""""Studies of the Opportunistic Infections Associated with the Acquired Immunodeficiency Syndrome"""""""", by proposing that neutralizing antibodies reactive with infectious stages of C. parvum would control cryptosporidiosis. Monoclonal antibodies were produced that defined neutralization-sensitive epitopes on sporozoites and merozoites. The research proposed in this competing renewal application continues that line of investigation and will test the hypothesis that cryptosporidiosis can be prevented and treated by administration of neutralizing antibodies reactive with sporozoite and merozoite stages of the organism. This will be accomplished by investigating the following specific aims. 1: Produce a replica of Cryptosporidium parvum sporozoite surface antigen defined by neutralizing monoclonal antibody 17.41. 2: Produce colostrum that neutralizes Cryptosporidium parvum sporozoites and merozoites. 3: Test neutralizing colostrum for ability to protect against challenge with Cryptosporidium parvum oocysts. 4: Test neutralizing colostrum for ability to terminate persistent Cryptosporidium parvum infection.
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